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Addex Therapeutics (SIX: ADXN), a
leading company pioneering allosteric modulation-based drug discovery
and
development, announced today achievement of a positive Proof of Concept
for its
lead metabotropic glutamate receptor 4 (mGluR4) positive allosteric
modulator
(PAM) compound series in a validated rodent model for multiple sclerosis
(MS).
MS is a chronic inflammatory demyelinating auto-immune disease that
affects the
central nervous system (CNS), leading to serious disability.

"We are very excited that this promising Addex mGluR4 PAM series may
offer a
differentiated approach to treating MS," said Professor Ursula
Grohmann, of
University of Perugia, Italy, in whose laboratories one of these
studies was
performed. "These data confirm our previous observations, using an
mGluR4 PAM
tool compound called PHCCC, which demonstrated efficacy in the industry
standard
neuroinflammation model of MS, the Relapsing-Remitting Experimental
Allergic
Encephalomyelitis (RR-EAE) model. In this study, the mGluR4 PAM
worked by
promoting regulatory T-cell (Treg) formation and reversing
pro-inflammatory T-cell release. Therefore, we believe that positive
modulation of mGluR4 could
potentially stop the destruction of myelin in MS in a robust and
durable
manner."

Addex lead chemical series is a highly selective orally available mGluR4
PAM and
shows good pharmacokinetic properties for potential once-daily dosing.
When
administered once a day for 3 weeks at 10, 30 and 60 mg/kg sc, Addex
mGluR4 PAM
demonstrated a dose-dependent, statistically significant reduction in
paralysis
(clinical score) and the relapse rate in the RR-EAE model of MS in
mice. The
presentation of these data is being planned for a major
international
conference.

"Current MS therapies are primarily focused on reinstating motor function
after
an inflammatory attack, preventing new attacks, and preventing or
treating
disability and symptoms, such as spasticity. In addition, most of
these
therapies are primarily based on immunomodulatory strategies, and have
serious
compliance-limiting side effects", noted Graham Dixon, CSO of
Addex
Therapeutics. "We believe a well-tolerated, oral mGluR4 PAM would
represent a
major advance in the treatment of MS because of the novel and
potentially
broader mechanism; having the potential to not only treat symptoms, but
slow
disease progression and offer neuroprotection. We are now rapidly advancing
this
lead series towards a clinical candidate and conducting experiments to
further
elucidate the biological role of mGluR4 PAM in MS."

"Moving the lead compound from this series into full development in 2012
clearly
illustrates our strategy of advancing innovative novel selective oral
small
molecule drug candidates against previously "undruggable" targets" said
Bharatt
Chowrira, CEO of Addex Therapeutics. "These data along with the
recently
announced data on the role of the mGluR4 PAMs in Parkinson's
disease, the
positive Phase 2 data for dipraglurant in Parkinson's disease
levodopa-induced dyskinesia, the two Phase 2 clinical trials being
conducted by our partner
Janssen, and our GABABR PAM program advancing towards an IND filing later
this
year, demonstrate the power of Addex platform that continues to
generate
multiple, novel high value product opportunities."

About Multiple Sclerosis

Multiple sclerosis, is an idiopathic inflammatory disease of the central
nervous
system, characterized pathologically by demyelination and subsequent
axonal
degeneration. The disease commonly presents in young adults and affects
twice as
many women as men. Common presenting symptoms include numbness, weakness,
visual
impairment, loss of balance, dizziness, urinary bladder urgency,
fatigue, and
depression. Approximately 2.5 million people worldwide are affected
with
prevalence ranging from 2 and 150 per 100,000, depending on the
country and
specific population. MS takes several forms. The most common affecting
around
85 per cent of everyone diagnosed with MS is relapsing remitting MS
(RRMS). It
means that symptoms appear (a relapse), and then fade away, either
partially or
completely (remitting). Secondary progressive MS (SPMS) is a stage of MS
which
comes after RRMS in many cases. Although the pathogenesis of MS is
complex and
not fully understood, it is believed that RRMS is characterized by
repeated
episodes of inflammation which eventually leads to the axonal
degeneration
through damage to, and loss of the myelin sheath characteristic of SPMS.
Given
the prominence of immune generated inflammation in MS, treatments
for the
disease have focused particularly on immunosuppressive
anti-inflammatory strategies. Currently approved treatments for RRMS are
only partially effective
in reducing MS relapses and in particular do not halt disability
progression.
As these drugs alter immune function, patients can experience
serious and
sometimes life threatening side effects (e.g. opportunistic infections,
emergent
malignancies, alopecia, cardiotoxicity and myelosuppression). Furthermore,
many
of these agents also require regular injection, or parenteral infusions
which
are uncomfortable and inconvenient for the patient.

The most significant unmet need in MS is for therapies that either
stop or
reverse neuronal damage and/or offer improved symptom relief
(such as
spasticity, pain, cognition). However, there is still demand for new
agents for
treatment of RRMS and for therapies with improved
safety/tolerability/side
effect profiles. The global MS therapeutics market was valued at over $9
billion
in 2011 and is forecast to grow to over $12 billion by 2019.

About mGluR4

High levels of glutamate are detected in patients with relapsing
remitting
multiple sclerosis. It has been suggested that glutamate may
affect
neuroinflammation via modulation of immune cells and/or neuroprotection
through
mGluR4 signaling. Therefore, pharmacological activation of mGluR4 may
represent
a novel therapeutic avenue addressing multiple aspects of MS
pathology. The
mGluR4 belongs to the Group III mGluRs (Class C G-Protein Coupled
Receptor) and
is negatively coupled to adenylate cyclase via activation of the
Gαi/o
protein. It is expressed primarily on presynaptic terminals, functioning
as an
autoreceptor or heteroceptor and its activation leads to
decreases in
neurotransmitter release from presynaptic terminals. The mGluR4 have
unique
distribution in key brain regions involved in multiple CNS
disorders. In
particular, mGluR4 is abundant in striato-pallidal synapses within the
basal
ganglia circuitry a key area implicated in movement disorders, like
Parkinson's
disease. In the immune system mGluR4 has been found on dendritic cells
(DCs).
Emerging data implicate mGluR4 in multiple indications such as
multiple
sclerosis, Parkinson's disease, anxiety, neuropathic and inflammatory
pain,
schizophrenia and diabetes.
Addex Therapeutics (www.addextherapeutics.com) discovers and
develops an
emerging class of small molecule drugs, called allosteric modulators, which
have
the potential to be more specific and confer significant therapeutic
advantages
over conventional "orthosteric" small molecule or biological drugs. The
Company
uses its proprietary discovery platform to address receptors and other
proteins
that are recognized as attractive targets for modulation of important
diseases
with unmet medical needs. The Company's two lead products are being
investigated
in Phase 2 clinical testing: dipraglurant (ADX48621, an mGluR5
negative
allosteric modulator or NAM) is being developed by Addex to treat
Parkinson's
disease levodopa-induced dyskinesia (PD-LID); and ADX71149 (mGluR2
positive
allosteric modulator or PAM) is being developed by our partner
Janssen
Pharmaceuticals Inc. to treat schizophrenia and anxiety seen in
patients
suffering from major depressive disorder. Addex also is advancing
several
preclinical programs including: GABABR PAM for overactive bladder and
other
disorders; mGluR4 PAM for Parkinson's, MS, anxiety and other
diseases. In
addition, Addex is applying its proprietary discovery platform to
identify
highly selective and potent allosteric modulators of a number of both
GPCR and
non-GPCR targets that are implicated in diseases of significant unmet
medical
need.

Disclaimer: The foregoing release may contain forward-looking statements
that
can be identified by terminology such as "not approvable",
"continue",
"believes", "believe", "will", "remained open to exploring", "would",
"could",
or similar expressions, or by express or implied discussions regarding
Addex
Therapeutics, formerly known as, Addex Pharmaceuticals, its
business, the
potential approval of its products by regulatory authorities, or
regarding
potential future revenues from such products. Such forward-looking
statements
reflect the current views of Addex Therapeutics regarding future events,
future
economic performance or prospects, and, by their very nature, involve
inherent
risks and uncertainties, both general and specific, whether known or
unknown,
and/or any other factor that may materially differ from the plans,
objectives,
expectations, estimates and intentions expressed or implied in such
forward-looking statements. Such may in particular cause actual results
with allosteric
modulators of mGluR2, mGluR4, mGluR5, GABABR or other therapeutic targets
to be
materially different from any future results, performance or
achievements
expressed or implied by such statements. There can be no guarantee
that
allosteric modulators of mGluR2, mGluR4, mGluR5, GABABR or other
therapeutics
targets will be approved for sale in any market or by any regulatory
authority.
Nor can there be any guarantee that allosteric modulators of mGluR2,
mGluR4,
mGluR5, GABABR or other therapeutic targets will achieve any particular
levels
of revenue (if any) in the future. In particular, management's
expectations
regarding allosteric modulators of mGluR2, mGluR4, mGluR5, GABABR or
other
therapeutic targets could be affected by, among other things, unexpected
actions
by our partners, unexpected regulatory actions or delays or
government
regulation generally; unexpected clinical trial results, including
unexpected
new clinical data and unexpected additional analysis of existing clinical
data;
competition in general; government, industry and general public
pricing
pressures; the company's ability to obtain or maintain patent or
other
proprietary intellectual property protection. Should one or more of these
risks
or uncertainties materialize, or should underlying assumptions prove
incorrect,
actual results may vary materially from those anticipated, believed,
estimated
or expected. Addex Therapeutics is providing the information in this
press
release as of this date and does not undertake any obligation to
update any
forward-looking statements contained in this press release as a result
of new
information, future events or otherwise, except as may be required by
applicable
laws.

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